Growth hormone secretagogue receptor type 1 (IPR003905)
Short name: GHS-R
Overlapping homologous superfamilies
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- Growth hormone secretagogue receptor type 1 (IPR003905)
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups [PMID: 12679517]. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [PMID: 8170923]. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [PMID: 8170923, PMID: 8081729, PMID: 15914470, PMID: 18948278, PMID: 16753280]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice [PMID: 12679517]. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [PMID: 23020293].
The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [PMID: 2111655, PMID: 2830256, PMID: 8386361].
Growth hormone (GH) release is thought to occur under the reciprocal regulation of two hypothalamic peptides (GH releasing hormone (GHRH) and somatostatin) via their engagement with specific cell surface receptors on the anterior pituitary somatotroph [PMID: 9092793, PMID: 8688086]. GH-releasing peptides (such as GHRP-6, and the nonpeptide mimetics, L-692, 429 and MK-0677) stimulate GH release through their activation of a distinct receptor, the GH secretagogue receptor (GHSR). This receptor couples to G-alpha-11 proteins.
- PR01417 (GHSRECEPTOR)